The present invention relates to implantable medical apparatus, especially radioactive stents for reducing the incidence of restenosis, and to a method for imparting radioactive properties to substrate materials such as stents, in particular by creating a surface layer of a radioactive isotope such as 32P.
A variety of apparatus and techniques have been developed for treating stenotic sites within body lumens. Among these apparatus and techniques are balloon dilitation and plaque excision. Among known balloon dilitation devices are coronary, peripheral vessel, bile duct and thorasic catheters. In balloon dilitation, a catheter equipped with an expandable balloon is threaded intravascularly to the site of atherosclerotic narrowing of the vessel. Balloon dilitation is known to have a good success rate in enlarging constricted body lumens, although there are various theories explaining the precise effect on constrictions causing this enlargement. Known plaque excision devices include ultrasound and mechanical excision devices. Plaque excision devices typically operate to remove or reduce in size at least a portion of the plaque associated with a stenotic region.
One complication of the known treatments of stenotic regions is restenosis (i.e. re-narrowing) of the vessel following treatment. Among the causes of such restenosis are, intimal hyperplasia (excessive tissue growth) and thrombus accumulation. It is known to reduce the occurrence of restenosis by placing a stent device at the site of the treated region. However, even with a stent in place, restenosis is known to occur in some treated sites, such as by the occurrence of excessive tissue growth.
The use of radiation to treat such excessive tissue growth also is known. A variety of techniques for delivering radiation to stenotic sites have been developed. One such technique delivers a radioactive dose via catheter, prior to stent implantation. An example of such a technique is described in Waksman et al., xe2x80x9cIntracoronary Radiation Before Stent Implantation Inhibits Neointimal Formation In Stented Porcine Coronary Arteries,xe2x80x9d Circulation, 1995:92:1383-1386. In this example, a low-dose radiation is delivered to coronary arteries from a radioisotope source, such as 192Ir or 90Sr/Y, via a catheter.
Another way of applying radiation to inhibit restenosis is through the use of radioactive stents. Examples of radioactive stents are described, in U.S. Pat. No. 5,059,166 and U.S. Pat. No. 5,213,561. Such known radioactive stents are made by various processes, such as by having a spring coil stent material irradiated so that it has become radioactive, implanting into a stent spring wire a radioactive ion such as phosphorous 32, alloying a stent spring wire with a radioactive ion, forming a stent coil from a radioisotope core material which is formed within an outer covering, and plating a radioisotope coating (such as gold 198) onto a stent spring material core.
A disadvantage of the known radioactive stents is undue complexity in the manufacturing process making the manufacture and handling of such stents difficult. Some known techniques of irradiating stent materials suffer the disadvantage of requiring the use of the neutron beam of a nuclear reactor in conjunction with an ion-implanter equipped with a sublimation source. One such example is described in Hehrlein, et al., xe2x80x9cPure xcex2-Particle-Emitting Stents Inhibit Neointima Formation in Rabbits,xe2x80x9d Circulation, 1996:93:641-645. Other known techniques involve high temperatures above the melting points of the materials being used to manufacture the stents, such as alloying.
Because of the complexity of the manufacturing processes, known manufacturing techniques suffer further disadvantages of being relatively unsuited for distributed manufacturing, in that the equipment costs are relatively high and the necessary manufacturing equipment such as wire forming equipment, alloying equipment, reactors and/or plating equipment is not understood to be readily transportable and requires operation by operators having skill in operating the equipment.
Yet another disadvantage of the known manufacturing techniques is the transport time between the site of manufacture and the site of use. Because of the need for transport of stents, at least some of the radioactive dose imparted during the manufacturing process is lost, since it is desirable to use if radioactive materials having relatively short half lives. With a radioisotope having a half-life of approximately fourteen days, such as 32P, approximately 78% of the radioactive dose remains after five days and 62% of the radioactive dose remains after ten days. Materials having shorter half lives are desired so that the radioactive effect of an implanted device dissipates relatively quickly, leading to greater control of the term of radioactive exposure of the patient. In order to compensate for the undesirable transport times and distances using the known techniques, users may need to resort to the use of radioactive materials having longer half lives, or to imparting greater radioactive doses to the stent material during manufacture, in order to compensate for the delays between manufacture and use such as in hospitals. This leads to increased inefficiency and cost.
Metal-phosphate coating processes using phosphoric acid solutions are also known for depositing coatings of to prevent corrosion, lubricate, prolong the life of metal surfaces, and improve paint coating adhesion. However, they have not been found well-suited to the specialized needs of medical applications such as stents or stent materials. Briefly described, the metal surface chemically reacts with a phosphate solution, forming a phosphate layer on the metal""s surface, which is either amorphous or crystalline depending on the operating conditions. A disadvantage of this coating technique is that the phosphate coating does not have the structural integrity required in medical uses and the has undesirable degrading or flaking characteristics. In addition, the transition metal (abbreviated herein as xe2x80x9cmxe2x80x9d) phosphate coating is generally a primary (i.e., mH2PO4), secondary (i.e., m2HPO4), or tertiary (i.e., m3PO4) metal phosphate, all of which are often hydrated (i.e., m3xe2x88x92nHnPO4. xH2O, where x=1, 2, 3, . . .).
From the above, it is apparent that there is a need for a more economical technique to manufacture radioactive stents, using less complex manufacturing processes and for an improved construction of a radioactive stent and for an improved method of manufacturing radioactive stents. It is therefore an object of the present invention to provide a method of making radioactive stents which can be performed at distributed sites, such as within or close to hospitals or other facilities where they may be used.
It is another object of the present invention to provide a method of making radioactive stents in a manner that could be done within the hospital or facility on an as-needed basis.
It is a further object of the present invention to provide a more economical method of making radioactive stents requiring less complicated techniques and apparatus.
Another object of the present invention is to provide a method of making a radioactive stent and for manufacturing a radioactive stent having increased accuracy in determination of the radioactive dose control, and achieving a greater degree of dosage uniformity that is independent of the stent geometry in the manufacturing process.
A further object of the present invention is to provide a stent coated with a radioisotope, which coating layer is generally insoluble as used for in vivo implantation.
Yet another object of the present invention is to provide a radioactive stent that includes a radioactive isotope material chemically bonded with a base material.
The present invention alleviates to a great extent the disadvantages of the known systems for manufacturing radioactive materials, such as stents for in vivo implantation by providing a method and apparatus for forming a layer containing a radioactive isotope received on a substrate or base material. A solution preferably including a polymerized chain including the radioactive isotope is provided. The solution is contacted with the substrate material and the substrate material receives the radioactive isotope containing layer.
In a preferred embodiment, the solution includes a polymerized orthophosphoric acid solution enriched with phosphorous-32 (32P). The substrate, preferably is a pre-formed medical stent, or alternatively a base material suitable for formation into a useful device, such as a stent. In operation, the substrate is immersed in the solution for a desired amount of time so as to impart a radioactive layer including phosphorous-32 to the substrate. The radioactive dosage is controlled by controlling the reaction time and other reaction conditions such as temperature and solution concentration.
Any stent shape or construction may be used in conjunction with the present invention.
The radioactive layer is formed on the surfaces in proximity to the solution, i.e. the surfaces which were contacted by solution. In embodiments where the stent is immersed in the solution, the radioactive layer is received on all the exposed surfaces. For example, where the stent has an open tubular structure, the radioactive layer is deposited on the inside and outside surfaces. In the preferred embodiment, where phosphorous-32 is used as the radioactive isotope, preferably a phosphorous-oxygen-phosphorous network bonding the phosphorous-32 to the substrate is formed.